BSVS mice were bred in the 1930's for susceptibility to salmonella and St. Louis encephalitis virus. We have found that these mice are markedly immunodeficient as compared to the BRVR mouse which was bred from the same outbred stock for resistance to these pathogens. Using a battery of nine antigens, we have shown that BSVS mice make normal IgM thymus-independent responses but make very low thymus-dependent IgG and delayed type hypersensitivity responses. Using one of these antigens, streptococcal Group A carbohydrate (GAC), we have found that BSVS mice show defects controlled by three different loci (H-2, IgCH, and Ir-GAC). The proposed experiments are designed to determine if the immunodeficiencies we have detected in this strain are causally related to its susceptibility to salmonella. To do this we will make use of four congenic BSVS lines now in their fifth backcross generation. Three of these congenic lines carry alleles from high responder strains at their H-2, IgCH, and Ir-GAC loci. The fourth congenic strain carries an allele that confers salmonella resistance on BSVS mice. The mechanism of action of this allele is still unknown and its elucidation has the potential of providing new insight into mechanisms of the immune respones and defense against infection. To investigate the relationship between immune deficiency and salmonella susceptibility we will compare the immune response potential and salmonella resistance of mice from these four congenic lines with that of BSVS mice. Other aspects of the immune response fo BSVS mice will also be studied. The immune response potential of their macrophages and T cells will be examined in detail since cellular immunity appears to play an important role in protection against salmonella infection. As these studies progress, our four congenic strains will become even more useful to us since they will facilitate investigations of the molecular and cellular mechanisms of the defects in BSVS immune responsiveness and salmonella resistance.